Deep Visual Proteomics elucidates α1-antitrypsin deficiency

Abstract

In a new study published in Nature, researchers have investigated the progression of the genetic liver disease α1-antitrypsin deficiency (AATD) in human tissue. Spatial proteomics by mass spectrometry and machine learning, via a technique termed Deep Visual Proteomics, was able to analyse the progressive proteotoxicity of AATD, a condition that causes misfolding of α1-antitrypsin in hepatocytes.

A set of formalin-fixed, paraffin-embedded biopsy samples and resections from patients with AATD across various fibrosis stages was used to map the proteome of hepatocytes undergoing AATD-induced proteotoxicity. Among other mechanistic observations, the researchers determined that α1-antitrypsin accumulation is mostly cell-intrinsic. They also identified a late-stage phenotype characterized by globular protein aggregates that precedes cell death.